Today, semisynthetic .beta.-lactam derivatives such as ampicillin, amoxicillin, cefaclor, cephalexin, cephadroxil and cephaloglycin are, in an industrial scale, prepared by chemical methods, for example by reacting an amino .beta.-lactam such as 6-aminopenicillanic acid, usually having its carboxyl group protected, with an activated side chain derivative, followed by the removal of the protecting group by hydrolysis. For example, ampicillin (6-D-.alpha.-aminophenylacetamido-penicillanic acid) can be prepared by reacting 6-APA, having a suitable protected carboxyl group, with D-phenylglycine acid chloride, followed by removal of the protecting group by hydrolysis. These reactions typically involve costly steps such as sub zero degree Celcius conditions and organic solvents like methylene chloride and silylation reagents.
Within the last years, there has been an increasing amount of publications concerning the possibility of enzymatic preparation of penicillins and cephalosporins by reaction of an acylating agent, be it in acid form or in activated form (for example, amide or ester) and the parent amino .beta.-lactam (for example, 6-APA or 7-ADCA). For example, enzymatic production of ampicillin from 6-APA and a D-phenyl-glycine derivative (such as a lower alkyl ester) is known from West German patent application having publication No. 2,163,792, Austrian Patent No. 243,986, Dutch patent application No. 70-09138, West German patent application having publication No. 2,621,618, European patent application having publication No. 339,751 and PCT patent application having publication No. 92/01061.
The enzymatic acylation of an amino .beta.-lactam with an acylating agent may be performed in the presence of a suitable amidase or acylase whereby the desired .beta.-lactam derivative is formed. The parent amino .beta.-lactam and the .beta.-lactam derivative have the same .beta.-lactam nucleus. In the .beta.-lactam derivative endproduct the 6-NH.sub.2 side chain of the penem parent .beta.-lactam or the 7-NH.sub.2 side chain of the cephem parent .beta.-lactam are acylated.
This reaction can be illustrated by the following reaction scheme I: